The study implies a 2 step study design. Patients are enrolled into 3 separate groups for melanoma, breast, and non-small cell lung cancer. In the first step, 21 patients per disease group are enrolled. If >=2 objective responses (SD, PR, or CR) out of 21 evaluable patients are observed, enrollment continues for other 45 patients as a whole, where response will be positively evaluated if >=10 patients will respond. If <2 objective responses out of 21 evaluable patients per disease group are observed, this(ese) group(s) will no longer be treated with temozolomide.

Inclusion Criteria:

• Cytological/histological diagnosis of either melanoma, non-small cell lung cancer and breast;
• Brain metastases >=1 cm presenting or in progression following >=4 weeks time interval free from previous malignancy-specific chemotherapy, hormone therapy, or other medical therapies;
• Magnetic resonance imaging suspected brain metastases; patients with brain lesion(s) not univocal as brain metastases must have negative radiolabeled leukocyte brain scan to rule out infectious non-malignant disease; all neuroradiological studies (baseline and treatment outcome evaluation), except for emergency exams must be performed after 10 days of unchanged schedule of dexamethasone, and obtained in the axial-coronal-sagittal planes in T1 and T2 before and after gadolinium enhancement.
• Presence of al least one bidimensionally measurable and not previously irradiated metastasis.
• Age <=70 years.
• Performance status 0-2 (ECOG-WHO scale).
• Blood leukocytes >=3.5 x 10^9/L and platelets >=100 x 10^9/L.
• Bilirubin <=25 M/L.
• Seric transaminases <=2 x upper limit of normal values.
• Creatinine <=150 M/L, creatinine clearance >=60 mL/min.
• Signed written informed consent.

Exclusion Criteria:

• Diabetes not allowing administration of adequate doses of dexamethasone at least during the first 2 months of treatment.
• Previous whole brain irradiation.
• Brain metastases eligible to neurosurgery or stereotactic radiation therapy.
• Previous or current malignancies at other sites with the exception of adequately treated in situ carcinoma of the cervix or basal and squamous carcinoma of the skin.
• Pregnant or nursing women.
• Acute infection requiring intravenous antibiotics.
• Severe vomiting or medical condition which could interfere with oral medication intake.
• Anticonvulsant chronic therapy.