The purpose of this study is to evaluate the local control rate on the target lesion at 6, 12, and 24 months after treatment with neoadjuvant stereotactic radiotherapy (SRS NEO group) compared to standard care, adjuvant stereotactic radiotherapy (POST OP SRS group).

This is a phase III, prospective, multicenter, randomized, two-group, controlled, open-label interventional study designed to evaluate the efficacy in terms of local progression-free survival of neoadjuvant stereotactic radiotherapy for brain metastases compared with adjuvant stereotactic radiotherapy.

The study population is composed of adult patients with 1 to 12 newly diagnosed brain metastases who require surgical treatment for the removal of at least one lesion.

The two therapeutic strategies studied in the trial are as follows:

• SRS NEO group (experimental group): stereotactic radiotherapy administered as neoadjuvant therapy (4 days ± 1 day before surgery to remove the brain metastasis).
• POST OP SRS group (control group): stereotactic radiotherapy performed adjuvantly (4 to 6 weeks after surgery to remove the brain metastasis).

Inclusion Criteria:

• Patients aged 18 years and older;
• Patients with 1 to 12 brain metastases on preoperative MRI, at least one of which (contrast enhancement of at least 1 cm) is accessible for the most complete possible resection (target lesion);
• Patients with a Karnofsky performance score of ≥ 70;
• Patients able to perform neurocognitive tests without assistance;
• Patients who understand the study and agree to attend all visits;
• Patients who have signed a written informed consent form;
• Affiliation with a social security system.

Exclusion Criteria:

• Patient who has already been treated with surgery, radiosurgery, and/or radiotherapy for the target brain metastasis;
• Medical contraindication to MRI;
• Patient with an estimated life expectancy of ≤ 3 months;
• Patients participating in another clinical trial, or who are in the exclusion period of another clinical trial;
• Patients unable to complete a self-administered questionnaire;
• Patients from a vulnerable population.

Due to the difference in the timing of stereotactic radiotherapy treatment (before or after surgery), blinding of patients or investigators will not be possible; however, magnetic resonance imaging will be analyzed by independent centralized review performed by neuroradiologists.