There is a lack of prospective trial data and consensus guidelines describing the use of Fractionated Stereotactic Radiation Therapy (FSRT) in the treatment of brain metastases. There has been no prospective dose escalation study performed to date to determine the maximum tolerated dose (MTD) in patients treated with FSRT. Prescription doses in the series described above ranged from 18 Gy to 42 Gy, delivered in 3 to 12 fractions. The results of this study will be used to plan future Phase II/III studies to determine the efficacy of different dose fractionation schedules of FSRT. The investigator team thus proposes a Phase I study to determine the feasibility and safety of FSRT in patients with brain metastases.

Inclusion Criteria:

• Pathologically proven diagnosis of a non-hematological malignancy other than small cell lung cancer within 5 years of registration
• Intact (unresected) brain metastases measuring ≥3 cm and ≤ 6 cm in largest dimension on gadolinium contrast enhanced MRI obtained within 30 days prior to registration OR Surgically resected brain metastasis for which postoperative stereotactic radiotherapy is indicated, with expected target measuring ≥3 cm and ≤6 cm in largest dimension
• Prior Whole Brain Radiation Therapy (WBRT) is allowed
• Age ≥ 18 years
• Women of childbearing potential and male participants must practice adequate contraception
• History/Physical examination within 30 days prior to registration
• Life expectancy >3 months
• Patients are allowed to enroll if previously treated to other lesions with Stereotactic Radiosurgery (SRS)
• Patients with multiple lesions are allowed, as long there is one dominant lesion that will be treated with FSRT. Other lesions may be treated concurrently with SRS or FSRT at the discretion of the treating physician but will not contribute to the study endpoints

Exclusion Criteria:

• Patients with definitive leptomeningeal metastases, based on cerebrospinal fluid (CSF) examination
• Plan for chemotherapy or targeted agents during treatment. Hormonal therapy, immunotherapy targeting PD-1/PD-L1 axis, and bone supportive therapy may be continued during treatment
• Contraindication to enhanced MRI imaging such as implanted metal devices. However, patients with implanted devices which are MRI compatible are allowed
• Patients with measurable brain metastasis resulting from small cell lung cancer and germ cell malignancy
• Uncontrolled intercurrent illness such as congestive heart failure, unstable angina, cardiac arrhythmia, and uncontrolled seizure activity
• Previous treatment of the target lesion with radiotherapy