This early phase I trial identifies the side effects of stereotactic radiosurgery before surgery in treating patients with cancer that has spread to the brain (brain metastases). Radiation may stimulate an anti-tumor immune response. Giving stereotactic radiosurgery before surgery may reduce the risk of the cancer coming back after surgery.

PRIMARY OBJECTIVE:

I. To determine the safety of pre-operative stereotactic radiosurgery (SRS) followed by surgery for brain metastasis.

SECONDARY OBJECTIVES:

I. To evaluate the immune niche in brain metastasis following SRS in the presence of low or high dose dexamethasone.

II. To evaluate the impact of pre-operative SRS on survival outcomes.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM A: Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive low dose dexamethasone orally (PO) or intravenously (IV) for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.

ARM B: Patients undergo SRS to the brain metastasis for 1-3 fractions over 1-5 days. Patients also receive high dose dexamethasone PO or IV for 2-21 days until the day of surgical resection. Patients then undergo surgical resection.

After completion of study intervention, patients are followed up for 120 days, and then every 12 weeks thereafter.

Inclusion Criteria:

• Age >= 18 years
• Prior or suspected diagnosis of malignancy
• Brain metastases visible on contrasted magnetic resonance imaging (MRI) brain
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy > 12 weeks as determined by the investigator
• Patients must have adequate organ function as determined by Neurosurgery to undergo surgery
• Willingness and ability of the subject to comply with scheduled visits, study procedures, and study restrictions
• Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation
• Patient must have a negative pregnancy test, be actively taking oral contraceptives or have undergone a hysterectomy

Exclusion Criteria:

• Patients on any immunosuppressive medication other than dexamethasone
• Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Human immunodeficiency virus (HIV)-positive
• Pregnant or nursing women are excluded
• Prior whole brain radiotherapy or SRS to the same site planned for surgery