Background With the increasing incidence of brain metastases (BMs), artificial intelligence models have shown promise in assisting with the detection and volumetric analysis of lesions at MRI. However, current models are limited in identifying small lesions and lack generalizability. Purpose To develop a generalizable deep learning system for detecting, segmenting, and longitudinally tracking BMs of any size at MRI. Materials and Methods In this retrospective study, a data-centric approach to deep learning model development was used. A multicenter dataset was collected, comprising pre- and/or posttreatment MRI scans from patients with BMs and MRI scans from patients with cancer without BMs (December 2015 to August 2023). Iterative data annotation by radiologists with systematic quality control increased the consistency of reference segmentations. A modified nnU-Net framework, with robust data preprocessing and augmentation, was used. Lesion-wise detection metrics and segmentation performance, Dice similarity coefficient, and normalized surface distance were evaluated. Results In total, 1985 scans from 1623 patients (mean age, 62.0 years ± 12.2 [SD]; 743 female patients, 157 patients of unknown sex), with 5552 BMs, were included. BMs were present in 64.8% of the scans (1286 of 1985), 36.0% (463 of 1286) of which were posttreatment scans. The model was trained on 1451 scans acquired on 30 different scanners. In internal testing ( = 223), sensitivity was 98.0% (95% CI: 96.3, 99.0; 449 of 458 lesions). In external testing ( = 311), sensitivity was 97.4% (95% CI: 96.2, 98.2; 935 of 960; = .58), with a mean of 0.6 false positives per patient. The sensitivity remained high for all lesion sizes, including those less than 3 mm in diameter (93.3% [95% CI: 89.1, 96.0]; 196 of 210). Median Dice similarity coefficient was 0.89 and 0.90 for the internal and external test datasets, respectively ( = .13). Median normalized surface distance was 0.99 for both datasets. Conclusion The deep learning system demonstrated high performance and generalizability in detecting and segmenting BMs of all sizes on pre- and posttreatment MRI scans. © RSNA, 2025