The purposes of this study are to find the highest dose of mafosfamide that can be given without causing severe side effects, to see how well the combination of these chemotherapy drugs and lower doses of radiation work to delay or stop the growth of the tumor, and to evaluate the pharmacokinetics (how the body handles) of Mafosfamide.

All children in the study will receive Regimen 1 chemotherapy. Children whose tumor is limited to one area at the beginning of the study will go on to have radiation therapy and then Regimen 2 chemotherapy. Children whose tumor was found in more than one part of the brain or in the cerebrospinal fluid at the beginning of the study will discontinue their treatment on this protocol after Regimen 1 chemotherapy.

Regimen 1 Chemotherapy - Those children with a normal CSF flow study at the beginning of the study will receive Regimen 1 chemotherapy along with mafosfamide. Those children with an abnormal CSF flow study will receive Regimen 1 without mafosfamide and a repeat CSF flow study will be performed at the completion of the first 10 weeks of treatment. If the CSF study reflects normal CSF flow, then intrathecal mafosfamide will be given during the second 10 weeks of Regimen 1. Regimen 1 is divided into two courses. Each course lasts about 10 weeks, for a total of 20 weeks of treatment. During Regimen 1 the patient will receive three medications (cyclophosphamide, vincristine, and cisplatin) that are given through the central venous line. The patient will also receive one medication that is given by mouth (etoposide). Cyclophosphamide, vincristine, cisplatin, and etoposide are all anticancer drugs that have been useful in the treatment of brain tumors.

The experimental drug, mafosfamide, will be injected into the spinal fluid. This will be given through either a spinal tap, the Ommaya reservoir, or both. Alternating mafosfamide between the spinal tap and the Ommaya reservoir may improve how well the drug works by making sure it spreads throughout the spinal fluid. If the patient has a VP or VA shunt ( specialized devices that relieve the pressure inside the head that comes from a block in the normal flow of spinal fluid), then the patient will not receive an Ommaya reservoir, and all doses of mafosfamide will be given through a spinal tap only.

The starting dose of mafosfamide will be a dose that has been safely given to older children. If that dose does not cause severe side effects, the next group of patients will receive a higher dose of mafosfamide. If severe side effects occur, the next group of patients will receive a lower dose of mafosfamide

During and at the end of Regimen 1, the patient will be evaluated for response of the brain tumor to treatment. A second operation may be necessary to remove more of the brain tumor. Children whose tumor had spread at the time they began this study have completed treatment at this point. Children whose tumor had not spread at start of the study will begin radiation therapy, if their tumor appears to be unchanged or shrinking after Regimen 1.

Radiation Therapy - The dose, location, and timing of radiation will depend on the age of the child at diagnosis, the location of his/her tumor, and the response of his/her tumor to Regimen 1 chemotherapy. The radiation treatments used in this protocol are designed in an attempt to reduce some of the side effects that usually occur after standard radiation therapy.

The child will receive radiation using a new technology called "conformal radiation". Conformal radiation is designed to reduce the amount of normal brain tissue that is exposed to high doses of radiation.

Regimen 2 Chemotherapy - After radiation therapy,the patient will receive additional chemotherapy, which will last about 20 weeks. Regimen 2 chemotherapy is the same as the Regimen 1 chemotherapy, except that the patient will not be given the drugs cisplatin and mafosfamide.

Pharmacokinetic (PK) studies will be performed with a total of 2 doses of intrathecal mafosfamide. PK studies tell us how the patient's body handles the study drug, mafosfamide. Sampling times (times when we collect cerebrospinal fluid for the PK studies) will be prior to drug administration and at 10 minutes, 2 hours, and 4 hours following drug administration. These studies will be performed after one dose of drug given through the spinal tap and after one dose of drug is given through the Ommaya reservoir. The pharmacokinetic study is optional and you can choose not to allow these samples to be drawn. Refusing the pharmacokinetic study will not affect the patient's participation/treatment on this study.

Inclusion/Exclusion Criteria:

• Age: < 3 years.
• Histology: Patient must have a histologically confirmed primary intracranial CNS medulloblastoma/PNET or other embryonal tumor (medulloepithelioma, ependymoblastoma, neuroblastoma, pineoblastoma), atypical teratoid/rhabdoid tumor, intracranial germ cell tumor, or choroid plexus carcinoma. Patients with M+ ependymoma are also eligible.
• Performance Status: Karnofsky or Lansky >= 30%
• Bone Marrow Function: All patients must have a Hgb >= 10 g/dl, ANC >= 1,500/mm3, and a platelet >= 100,000/mm3. If the patient has a positive bone scan, then a pretreatment bone marrow aspirate and biopsy must be free of tumor.
• Hepatic/Renal Function: All patients must have adequate hepatic (total bilirubin < 1.5 mg/dl, SGPT < 5x normal), and renal (normal serum creatinine for age or technetium clearance > 40/ml/min/m2) function.
• Prior Therapy: Patients may not have received prior radiotherapy or chemotherapy, with the exception of steroids. Patients must not be receiving any other investigational agents. (Patients may receive investigational agents for supportive care 30 days after completion of all mafosfamide therapy.)
• Surgery: Patients must begin protocol therapy within 35 days of definitive surgery.
• Central Line: Patients must be willing to have a central line.
• CSF flow: Patients must be willing to have a CSF flow study to determine whether or not they will receive intrathecal chemotherapy. Patients without a VP or VA shunt must be willing to have an Ommaya reservoir if their CSF flow study does not show any evidence of obstruction to or compartmentalization of flow. Patients with obstruction to or compartmentalization of CSF flow on their initial flow study must be willing to have a repeat flow performed within the initial 10 weeks of induction therapy, ideally during weeks 8-10. If a repeat flow study shows resolution of obstruction or compartmentalization, patients are expected to begin intrathecal mafosfamide during Regimen 1 course 2 of therapy. Patients without a VP or VA shunt who have resolution of normal flow should additionally have an Ommaya reservoir placed.